Pregnancy Outcomes in Patients with Early-Onset Idiopathic Chronic Pancreatitis.

BACKGROUND: Early-onset idiopathic chronic pancreatitis (EOICP) is a disease that affects young individuals. Data on pregnancy outcomes in EOICP are limited. AIM: To assess the pregnancy outcomes in patients with EOICP and the effect of pregnancy on the course of EOICP. METHODS: Patients with EOICP with disease onset before their pregnancy were recruited. Data regarding demographic variables, disease duration, pregnancy outcomes, and course of illness were noted. RESULTS: 50 patients were included in the study contributing to a total of 86 pregnancies. The mean age of onset of symptoms and at the time of delivery was 17.95 (5.71) and 23.44 (4.28) years, respectively. Gestational diabetes (GD) and gestational hypertension (GH) noted in one (1.5%) each. 3 (4.5%) pregnancies were preterm. 19 (22.1%) pregnancies did not have successful outcomes (7 (8.1%) were induced abortions). 12 (15.2%) pregnancies had spontaneous pregnancy losses. 8 (10.1%) were spontaneous abortions and 4 (5.1%) were stillbirths. Of 67 successful pregnancies, 33 (49.3%) pregnancies were delivered by LSCS. Compared to average rates of LSCS in India, this was significantly higher (21.5% vs 49.3%-p ≤ 0.001). The average birth weight was 2.87 (0.48) kg. There was one (1.5%) neonatal death. Compared to the published Indian data, there was no significant difference in the incidence of spontaneous pregnancy losses, GD, GH, preterm labor, and birth weight. Pancreatic pain was reported by 21 (42%) women in total 27 (31.4%) pregnancies. There was no difference in maternal or fetal outcomes between pregnancies with or without pancreatic pain. There were no pancreatitis-related complications reported during the pregnancies. CONCLUSION: The present study shows that mothers affected with EOICP have pregnancy outcomes similar to healthy women in India.

Smoking Is Associated with Worse Clinical Outcomes in Chronic Pancreatitis.

BACKGROUND: Tobacco smoking is a known risk factor for progression of chronic pancreatitis (CP). AIM: We compare clinical outcomes of CP patients with current or former smoking with those who have never smoked. METHODS: We reviewed all patients with followed at our Pancreas Center from 2016 to 2021, comparing the demographics, clinical features, comorbidities, outcomes, and resource utilization between smokers and non-smokers. RESULTS: Of 439 CP patients, 283 were smokers (125 current, 158 former). Significantly more smokers were men (58.3% vs 40.4%), with alcoholic CP (45.5% vs 12.1%), chronic abdominal pain (77.7% vs 65.4%), anxiety and depression (22.6% vs 14.1% and 38.9% vs 23.1%), and with more local pancreatic complications [splanchnic vein thrombosis (15.7% vs 5.13%), pseudocyst (42.7% vs 23.7%), biliary obstruction (20.5% vs 5.88%)], exocrine pancreatic insufficiency (65.8% vs 46.2%), hospitalizations (2.59 vs 1.75 visits), and emergency department visits (8.96% vs 3.25%). Opioid and neuromodulator use were significantly higher (59.2% vs 30.3% and 58.4% vs 31.2%). Current smokers had worse outcomes than former smokers. Multivariate analysis controlling for multiple factors identified smoking as an independent predictor of chronic abdominal pain (OR 2.49, CI 1.23-5.04, p = 0.011), opioid (OR 2.36, CI 1.35-4.12, p = 0.002), neuromodulators (OR 2.55, CI 1.46-4.46, p = 0.001), and non-opioid-controlled medications (OR 2.28, CI 1.22-4.30, p = 0.01) use, as well as splanchnic vein thromboses (OR 2.65, CI 1.02-6.91, p = 0.045) and biliary obstruction (OR 4.12, CI 1.60-10.61, p = 0.003). CONCLUSION: CP patients who smoke or formerly smoked have greater morbidity and worse outcomes than non-smokers.

Homozygosity of short VNTR lengths in the CEL gene may confer susceptibility to idiopathic chronic pancreatitis.

OBJECTIVE: The carboxyl-ester lipase (CEL) gene contains a variable number of tandem repeats (VNTR) region. It remains unclear whether the number of repeats in the CEL VNTR is related to the risk of pancreatic diseases. The aim of this study was to investigate whether CEL VNTR length is associated with idiopathic chronic pancreatitis (ICP), alcoholic chronic pancreatitis (ACP), or pancreatic cancer in a cohort of Chinese patients. METHODS: CEL VNTRs were genotyped in patients diagnosed with ICP (n = 771), ACP (n = 222), or pancreatic cancer (n = 263), and in healthy controls (n = 927). CEL VNTR lengths were determined using a screening method combining PCR and DNA fragment analysis. RESULTS: Overall, the CEL VNTR lengths ranged from 5 to 22 repeats, with the 16-repeat allele ('normal' size, N) accounting for 73.82% of all observed alleles. The VNTR allele frequencies and genotype distributions were not significantly different between healthy controls and patients with ACP or pancreatic cancer. For the ICP group, allele frequencies did not differ significantly from the controls, while the frequency of the SS genotype (homozygosity for 5-15 repeats) was significantly higher in the patients (4.67%) than in the controls (1.94%) (p = 0.0014; OR = 2.47; 95% CI = 1.39-4.39). CONCLUSIONS: There were no associations between the CEL VNTR length and ACP or pancreatic cancer. However, homozygosity for short VNTR lengths may confer susceptibility to ICP.

Sequencing of the complex CTRB1-CTRB2 locus in chronic pancreatitis.

BACKGROUND: /Objectives: A recent Genome-wide Association Study (GWAS) in alcoholic chronic pancreatitis (ACP) identified a novel association with the CTRB1-CTRB2 (chymotrypsinogen B1, B2) locus, linked to a 16.6 kb inversion that was confirmed in non-alcoholic chronic pancreatitis (NACP). Moreover, recent findings on the function of CTRB1 and CTRB2 suggest a protective role in pancreatitis development. The aim of the present study was to investigate the CTRB1-CTRB2 locus for rare genetic variants associated with chronic pancreatitis (CP). METHODS: We analyzed 134 patients with ACP and 203 patients with NACP and compared them to up to 258 healthy controls. Genotyping was performed with polymerase chain reaction, followed by Sanger sequencing of all exons and the exon-intron-boundaries of CTRB1 and CTRB2. Finally, in silico analyses of the identified variants were conducted. RESULTS: None of the seven rare missense variants or the single 5'-UTR variant in CTRB1 and CTRB2 was associated with ACP or NACP. In silico analysis predicted that variant p. Trp5Leu in CTRB1 and variant c.-4C > T in CTRB2 might alter protein expression and variants p. Asp222His in CTRB1 and p. Ala247Thr in CTRB2 might affect protein function. However, all of these variants were also described in public databases. CONCLUSIONS: The present study did not reveal an association of rare variants in CTRB1 and CTRB2 with ACP or NACP. Although rare missense variants were almost exclusively found in patients, only four variants were predicted to affect protein expression or function. Thus, a major influence of rare variants in the CTRB1-CTRB2 locus on CP development is unlikely.

Risk factors and nomogram for diabetes mellitus in idiopathic chronic pancreatitis.

BACKGROUND AND AIM: Diabetes mellitus (DM) is a common complication of idiopathic chronic pancreatitis (ICP), which impairs the quality of life for patients. This study aimed to identify risk factors and develop nomogram for DM in ICP to help early diagnosis. METHODS: Idiopathic chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were included. Cumulative rates of DM were calculated by Kaplan-Meier method. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on training cohort, risk factors for DM were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: Totally, 1633 patients with ICP were finally enrolled. The median follow-up duration was 9.8 years. DM was found in 26.3% (430/1633) of patients after the onset of CP. Adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct were identified risk factors for DM development. The nomogram achieved good concordance indexes in the training and validation cohorts, respectively, with well-fitted calibration curves. CONCLUSIONS: Risk factors were identified, and nomogram was developed to determine the risk of DM in ICP patients. Patients with one or more of the risk factors including adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct have higher incidence of DM.

No significant enrichment of rare functionally defective CPA1 variants in a large Chinese idiopathic chronic pancreatitis cohort.

Rare functionally defective carboxypeptidase A1 (CPA1) variants have been reported to predispose to nonalcoholic chronic pancreatitis, mainly the idiopathic subtype. However, independent replication has so far been lacking, particularly in Asian cohorts where initial studies employed small sample sizes. Herein we performed targeted next-generation sequencing of the CPA1 gene in 1,112 Han Chinese idiopathic chronic pancreatitis (ICP) patients-the largest ICP cohort so far analyzed in a single population-and 1,580 controls. Sanger sequencing was used to validate called variants, and the CPA1 activity and secretion of all newly found variants were measured. A total of 18 rare CPA1 variants were characterized, 11 of which have not been previously described. However, no significant association was noted with ICP irrespective of whether all rare variants [20 out of 1,112 (1.8%) in patients vs. 24 out of 1,580 (1.52%) in controls; P = 0.57] or functionally impaired variants [three out of 1,112 (0.27%) in patients vs. two out of 1,580 (0.13%) in controls; P = 0.68] were considered.

[Hereditary pancreatitis]. / Dziedziczne zapalenie trzustki.

Hereditary pancreatitis (HP) is a rare, heterogeneous familial disease and should be suspected in any patient who has suffered at least two attacks of acute pancreatitis for which there is no underlying cause and unexplained chronic pancreatitis with a family history in a first- or second degree relative. with an early onset, mostly during childhood. Genetic factors have been implied in cases of familial chronic pancreatitis. The most common are mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). The inflammation results in repeated DNA damage, error-prone repair mechanisms and the progressive accumulation of genetic mutations. Risk of pancreatic adenocarcinoma is a major concern of many patients with hereditary chronic pancreatitis, but the individual risk is poorly defined. Better risk models of pancreatic cancer in individual patients based on etiology of pancreatitis, family history, genetics, smoking, alcohol, diabetes and the patient's age are needed.

Natural History, Clinical Characteristics, and Outcomes in Idiopathic Chronic Pancreatitis.

Background and Aims: Chronic pancreatitis (CP) is a fibroinflammatory syndrome of the pancreas associated with pain and poor quality of life. It has toxic and genetic risk factors but can also be idiopathic. The natural history of idiopathic CP (ICP) is not well-known. Therefore, we studied clinical characteristics and outcomes of these patients followed in our Pancreas Center. Methods: Review of CP patients between January 1, 2016, and April 30, 2021. Patients were divided into 2 groups based on diagnosis, ICP vs non-ICP. CP patients with a smoking history were placed in the non-ICP group. Statistical analysis was performed to identify differences in demographics, comorbidities, complications, controlled medications, and resource utilization. Results: Out of 450 patients, 101 (22%) were diagnosed with ICP and 349 (78%) were non-ICP. ICP patients were mainly female (59.4% vs 40.5%; P = .005), had less comorbid anxiety (10.5% vs 22.1%; P = .002), depression (24.2% vs 35.8%; P < .001), disability (13% vs 16.3%; P = .021), exocrine pancreatic insufficiency (45.3% vs 62.6%; P = .004), splanchnic vein thrombosis (1.04% vs 14.9%; P < .001), pseudocysts (16.7% vs 41.6%; P < .001), and biliary obstruction (3.12% vs 19.2%; P < .001). They underwent less abdominal imaging (2.63 vs 3.42; P = .048) and endoscopic retrograde cholangiopancreatography (0.88 vs 1.32; P = .030). They also had less opioid use (29.6% vs 54.4%; P < .001), gabapentinoid use (34% vs 52.3%; P = .002), and celiac blocks (7.22% vs 16.1%; P < .041). Conclusion: Our study demonstrates that the clinical course of ICP is less morbid compared to non-ICP. This study specifically removes smoking, a significant risk factor for CP, to study a truly idiopathic cohort.

Genetic polymorphisms in phase II metabolizing enzymes in alcoholic and idiopathic chronic pancreatitis: Indian scenario.

AIM: To study polymorphisms in glutathione-S-transferases (GST-T1, GST-M1, GST-P1) and uridine-5'-diphosphate-glucuronosyl-transferases (UGT1A7) genes and the risk of developing chronic pancreatitis (CP) associated with these polymorphisms. METHODS: This study included 49 alcoholic and 51 idiopathic chronic pancreatitis patients, 50 alcohol addicts and 50 healthy controls. Polymorphism(s) in GST-T1 and GST-M1 genes were assessed by multiplex polymerase chain reaction (PCR), while PCR-radiofrequency lesioning (RFLP) was employed to assess the same in GST-P1 and UGT1A7 genes. The differences in polymorphism frequency between groups and the risk of developing pancreatitis were assessed by the odds ratio. RESULTS: Strong association of the null genotype of GST-T1 with CP susceptibility was observed. Alcoholics with the Val allele of GST-P1 have higher chances of having pancreatitis. Idiopathic pancreatitis patients with higher age at the onset of pain were found to have the null genotype of GST-M1. CONCLUSION: Alcoholics with the null genotype of the GST-T1 gene and the Valine allele of the GST-P1 gene are at a higher risk of developing CP. Thus, genotyping of these genes may serve as an important screening tool for the identification of high-risk groups among alcoholics.

Risk factor analysis and nomogram development for steatorrhea in idiopathic chronic pancreatitis.

OBJECTIVES: Steatorrhea, a sign of severe pancreatic exocrine insufficiency (PEI), is related to consequences caused by pancreatitis. This study aimed to identify predictors and to construct a nomogram for steatorrhea in idiopathic chronic pancreatitis (ICP). METHODS: ICP patients admitted to our hospital from January 2000 to December 2013 were enrolled in this retrospective-prospective cohort study and randomly assigned to the training and validation cohorts. The cumulative rate of steatorrhea was calculated. A Cox proportional hazard regression model was used to identify predictors for steatorrhea and construct the nomogram. Internal and external validation of the nomogram was then performed. RESULTS: There were 1633 ICP patients enrolled, with a median follow-up duration of 9.8 years and 20.8% (339/1633) of patients developed steatorrhea following onset of ICP. Steatorrhea was observed in 93, 115, and 133 patients at 1, 3, and 5 years following diagnosis of CP, with a cumulative rate of 6.5% (95% confidence interval [CI] 5.1%-7.9%), 8.0% (95% CI 6.2%-9.8%), and 9.3% (95% CI 6.6%-12.0%), respectively. Male sex (hazard ratio [HR] 2.479, P < 0.001), diabetes mellitus at/before diagnosis of ICP (HR 2.274, P = 0.003), and aged less than 18 years at onset of ICP (HR 0.095, P < 0.001) were identified risk factors for steatorrhea. Initial manifestations were associated with development of steatorrhea. The nomogram was proven to have good concordance indexes. CONCLUSIONS: We identified predictors and developed a nomogram for predicting steatorrhea in ICP. It was recommended that high-risk populations be followed up closely, which might contribute to the early diagnosis and treatment of PEI.

IVS8-5T Allele of CFTR is the Risk Factor in Chronic Pancreatitis, Especially in Idiopathic Chronic Pancreatitis.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator IVS8-5T gene variation appears to be associated with a higher risk of chronic pancreatitis (CP); however, there is inconsistency between previous reported studies. Here, we performed a meta-analysis to investigate this relationship. MATERIALS AND METHODS: PubMed and WANFANG databases were searched for the case-control studies that contained Patients with CP with IVS8-5T variation. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relevance of IVS8-5T gene variation and CP. RESULTS: Analysis showed that the frequency of the 5T allele was significantly higher in CP subjects than that in control subjects (OR = 1.43, 95% CI: 1.13-1.81, I2 = 1.2%). Based on the subgroup analysis stratified by etiology, the 5T allele was associated with a higher risk of idiopathic chronic pancreatitis (ICP) (OR = 1.80, 95% CI: 1.18-2.76, I2 = 0.0%) and not alcoholic CP (OR = 2.14, 95% CI: 0.98-4.66, I2 = 0.0%). Further study indicated that the 5T allele was related to higher ICP prevalence in the European population (OR = 1.79, 95% CI: 1.06-3.03, I2 = 0.0%). In contrast, there was no significant difference between ICP subjects and healthy controls within the Asian population (OR = 1.84, 95% CI: 0.91-3.72, I2 = 38.0%). CONCLUSIONS: Cystic fibrosis transmembrane conductance regulator IVS8-5T is a risk factor in patients with CP. IVS8-5T variation may play a significant role in the occurrence of ICP, especially in the European population.

Chronic pancreatitis in Eastern India: Experience from a tertiary care center.

There is a wide variation in the clinical presentation of chronic pancreatitis (CP) in the different parts of India. Data regarding the clinical profile of CP from eastern India are scarce. We describe the clinical and demographic profiles of patients with CP in eastern India. Consecutive patients were evaluated for the clinical presentation, etiology and complication of CP. One hundred and thirty-nine patients with CP (mean age 39.57±14.88 years; M/F 3.48:1) were included. Idiopathic CP (50.35%) was the most common etiology followed by alcohol (33.81%); 68.34% had calcific CP and 31.65% had noncalcific CP. The median duration of symptoms was 24 (1-240) months. Pain was the most common symptom, being present in 93.52% of the patients. Diabetes, steatorrhea and pseudocyst were present in 45.32%, 14.38% and 7.19% of the cases, respectively. Moderate to severe anemia was revealed in 16.53% of the patients. Benign biliary stricture was diagnosed in 19.42% of the cases (symptomatic in 6.47%). The common radiological findings were the following: pancreatic calculi (68.34%), dilated pancreatic duct (PD) (58.99%), parenchymal atrophy (25.89%) and PD stricture (23.74%). In our center, idiopathic CP followed by alcoholic CP was the most frequent form of CP. Tropical CP was distinctly uncommon.

Association between F508 deletion in CFTR and chronic pancreatitis risk.

BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) has been reported to influence individual susceptibility to chronic pancreatitis (CP), but the results of previous studies are controversial. AIMS: We performed a study to demonstrate the relationship between CFTR and CP. METHODS: We searched PubMed, Scopus, and Embase for studies of patients with CP. Seven studies from 1995 to 2016 were identified, and included 64,832 patients. Pooled prevalence and 95% confidence intervals (CIs) were calculated. RESULTS: F508 deletion in CFTR was significantly positively associated with CP risk in the overall analysis (odds ratio [OR]=3.20, 95% CI: 2.30-4.44, I2=31.7%). In subgroup analysis stratified by ethnicity, F508 deletion was significantly associated with CP risk in Indian populations, using a fixed effects model (ORs=5.45, 95% CI: 2.52-11.79, I2=0.0%), and in non-Indian populations, using a random effects model (ORs=3.59, 95% CI: 1.73-7.48, I2=60.9%). At the same time, we found that Indians with F508 deletion had much higher CP prevalence than non-Indians. Interestingly, F508 deletion was also associated with CP and idiopathic CP risk in subgroup analysis stratified by aeitiology, using the fixed effects model. CONCLUSIONS: Based on current evidence, F508 deletion is a risk factor for CP, and Indians with F508 deletion have much higher CP morbidity.